Artificial kidney for frequent (daily) hemodialysis

ABSTRACT

A hemodialyzer apparatus comprises a reusable dialyzer membrane as well as reusable blood flow path and dialysis flow path units. The apparatus automatically primes itself and makes dialysis solution from dry chemicals, concentrates, and fresh water which is provided to the apparatus. Also, after use, the apparatus automatically prepares cleaning and rinsing solution for the cleaning and rinsing of the dialyzer membrane as well as the dialyzate and blood flow path means, to provide a system which is so simplified in terms of automatic operation that it may be usable for daily dialysis at home.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a division of U.S. application Ser. No. 08/335,102, filed Nov.7, 1994, which is a division of U.S. application Ser. No. 08/155,993,filed Nov. 22, 1993, now U.S. Pat. No. 5,484,397 which, in turn, is adivision of U.S. application Ser. No. 07/748,036, filed Aug. 21, 1991,now U.S. Pat. No. 5,336,165 issued Aug. 9, 1994.

BACKGROUND OF THE INVENTION

The proposed invention is an artificial kidney system for frequent,typically daily, hemodialysis intended to improve significantlyhemodialysis therapy and prognosis, to make home hemodialysis feasibleand even attractive to a much broader base of patients, and to decreasethe overall cost burden for patients with chronic renal failure.

There are approximately 120,000 patients on dialysis in the UnitedStates, almost 400,000 worldwide. Most of them dialyze in hemodialysiscenters and approximately 17% are on home peritoneal dialysis with lessthat 3% on home hemodialysis. In-center hemodialysis is performed threetimes per week for between two and four hours. The more "physiologic"four times per week dialysis sessions are used only with patients withsevere intolerance to three times weekly dialysis, mostly related tocardiovascular instability. Home hemodialysis is also universallyperformed three times weekly.

It is well accepted in the nephrology community that the optimalfrequency of intermittent hemodialysis for chronic renal failure has notyet been established. The first patients treated by Scribner et al., in1959 (Scribner B H, Buri R, Caner J E Z, Hegstrom R M, Burnell J M: "Thetreatment of chronic uremia by means of intermittent hemodialysis: apreliminary report." Trans Am Soc Artif Intern Organs 1960; 6: 114-122)received hemodialysis at intervals of five to seven days for 20-24hours. However, the patients manifested uremic symptoms which could onlybe relived by increasing the frequency of dialysis (Hegstrom R M, MurreyJ S, Pendras J P, Burnell J M, Scribner B H: "Two years experience withperiodic hemodialysis in the treatment of chronic uremia." Trans Am SocArtif Intern Organs 1962; 8: 266-275). Later, in the 1960's, twiceweekly dialyses were used routinely. During the 1970's, three timesweekly dialyses became more popular as it was realized that the overallresults were better than with twice weekly schedule. Presently, twodialysis per week are applied only in patients with well preservedresidual renal function. Three dialyses per week is considered astandard schedule in the majority of dialysis centers as it seems toyield an adequate or acceptable clinical status in the majority ofpatients.

The amount of time consumed by transportation to and from the center,and the dialysis procedure itself, is mostly tolerable for the patientswho perform three sessions per week. Consequently, only those patientswho experience unbearable intolerance of body fluid volume fluctuations,and the associated symptoms, agree to more frequent (four times weekly)dialysis sessions. For home dialysis patients, more frequent dialysisthan three times per week would mean more stress on the relatives whohelp with set-up and who monitor the patient and, of course, on thepatient who does most of the work for set-up, tear-down, and cleaning.

An arteriovenous fistula, either classic or Gore-tex, is the mostcommonly used method of creating blood access for hemodialysis. For eachdialysis session, the fistula must be punctured with large bore needlesto deliver blood into, and return blood from, the artificial kidney(dialyzer). The punctures with these large bore needles are painful,even with the use of anesthetics. It is natural that the patients wouldlike to have punctures done as infrequently as possible. Also, there isa general perception (although no proof) that frequent punctures aredetrimental to the fistula longevity. Three times weekly dialysisschedule seems to be a reasonable compromise.

Last, but not least, the current Medicare reimbursement schedule for anyform of dialysis is based on three hemodialyses per week done in-center.This allows the providers to maintain a small but acceptable profitmargin. More frequent dialysis would mean a substantial increase in theproviders' cost of treatment and result in a net loss to the providerfor any patient receiving more than three treatments per week.

Existing hemodialysis systems consist fundamentally of two halves; onecomprising the extracorporeal blood circuit (the blood flow path) andthe other comprising the dialysate circuit or flow path. Typically, theentire blood circuit is disposable and comprises: 1) an arterial andvenous fistula needle, 2) an arterial (inflow) and venous (outflow)blood line, 3) a hemodialyzer, 4) physiologic priming solutions (saline)with infusion set, and 5) an anticoagulant (heparin or citrate). Thearterial needle accesses blood from the patient's fistula and isconnected to the arterial blood tubing set, which conveys blood to thedialyzer.

The arterial line comprises: a pumping segment with interfaces to ablood pump (rotary or peristaltic) on the hemodialysis machine, pressuremonitoring chambers including tubing which interfaces to pressuretransducers on the machine to monitor the pressure pre-pump and/or postpump, inlet ports for saline and anticoagulant, and one or moreinjection sites for drawing blood or injecting drugs.

The hemodialyzer typically comprises a case which encloses a bundle ofhollow fiber semi-permeable membrane. The blood is circulated on oneside of the membrane while dialysis solution is circulated on the other,so that the two never come into direct contact. Uremic toxins diffuseout of the blood and into the dialysis solution owing to theconcentration gradient. Excess water in the patent's blood enters thedialysate as a result of a pressure gradient. The membrane is made fromeither cellulose or synthetic polymers.

The venous line and needle carry the newly dialyzed blood away from thedialyzer and back into the patient's circulatory system via a puncturesite slightly closer to the heart than the arterial needle site. Thevenous set is comprised of a pressure monitoring chamber with tubingleading to another pressure transducer in the machine, injection sites,and a segment of tubing which interfaces to an air detection assembly inthe machine in order to prevent air emboli during treatment.

Dialysis solution is typically prepared continuously on-line inpresent-day machines by combining; 1) water which has first beenpurified by a separate water treatment system and, 2) liquidconcentrates of electrolytes. Over the past decade the dialysateconcentrates have evolved from a single formulation which containedacetate as the physiologic buffering agent for the correction ofcirculatory acidosis, to two containers where bicarbonate replacesacetate as the buffering agent, and must be kept separate due to itschemical incompatibility with calcium and magnesium. Two proportioningpumps are therefore required, the first to mix the bicarbonateconcentrate with water and the second to proportion this mixture withthe concentrated electrolytes to achieve the final, physiologicallycompatible solution.

The machine continuously monitors the pressure at the blood inlet andoutlet sides of the dialyzer (by way of the pressure transducersconnected to the blood sets) as well as in the dialysate circuit. Viamicroprocessors, the system calculates the transmembrane pressure (TMP)which determines the amount of water transmission through the membrane.These machines also have sophisticated means of measuring the amount ofdialysis solution entering and dialysate leaving the dialyzer, whichallows the calculation of net water removal from the patient(ultrafiltration). By electronically comparing the amount of waterentering or leaving the blood with the transmembrane pressure, thesystem is able to control actively the water removed from the patient toa desired target previously programmed into the system. Whenlow-water-transmission cellulosic membranes are employed, negativepressure must be generated on the dialysate side of the membrane by themachine in order to accomplish sufficient water removal. Because suctionmay be applied to the dialysate as it transits the dialyzer, it mustfirst be placed under a greater vacuum in a degassing chamber so thatair bubbles are not generated within the dialyzer that would causeerrors in the calculation of ultrafiltration by the flow sensors andalso reduce the efficiency of the dialyzer. On the other hand, whenhigh-water-transmission, synthetic membranes are used, it is frequentlynecessary to apply positive pressure on the dialysate side to controlthe rate of ultrafiltration.

In order to understand fully the advantages of the proposed system it isnecessary to also understand the existing procedures. The first step insetting up is typically to prepare the dialysate. For the concentrate ofelectrolytes no preparation is necessary; a hose from the machine issimply inserted into a jug just as it comes from the manufacturer. Thebicarbonate, however, is most often bought as a powder because of itsinstability in solution, and it must first be mixed in a jug withpurified water. When the concentrates are ready, the machine is turnedon so that the temperature and conductivity have time to come into theirsafe operating ranges.

Next, all components of the extracorporeal blood circuit are unpacked,connected together using aseptic technique and threaded onto the machineby matching the respective components to their hardware interfaces. Theair is primed out of the circuit by connecting sterile normal saline tothe arterial tubing set via an IV administration set, and starting theblood pump on the machine. Agitation of the dialyzer is frequentlynecessary to remove completely the air from it, and this process cantake 10-15 minutes. Some practitioners are able to both prime thecircuit and rinse the blood back at the end of treatment with a singleone liter bag of saline, but most often, two one-liter bags arerequired.

If the dialyzer is being reused, a chemical sterilizing solution will bepresent in the dialyzer instead of air, and this must first be rinsedout. In this case, additional steps are required. Once the bulk of thedisinfectant and air are primed out of the circuit, the arterial andvenous blood lines are usually connected together to form a closed loop.Thereafter, the enclosed solution is recirculated countercurrently tothe dialysate, thus causing any remaining contaminants to dialyze acrossthe membrane, into the dialysate, and down the drain. Before the patentcan be connected to this primed extracorporeal circuit, the primingfluid must be manually tested for residual sterilizing chemicals (e.g.formaldehyde) by a calorimetric chemical assay to assure they are atsafe levels.

At this point the arterial and venous needles are placed in thepatient's blood access site, and the pump is started, causing thepriming solution to the displaced into a drain container. When bloodapproaches the venous tubing set, the pump is stopped. The set isconnected to the venous needle, and the pump speed is gradually orrapidly elevated to the prescribed value. Blood flow rates of 175-450ml/min are typical, being limited by the needle size and access anatomy.The faster the blood flow rate, the faster the dialysis procedure can beaccomplished, thereby benefitting both patient and physician (as long aswater removal rates are tolerable). However, the needles, which in thepast have in part determined the allowable blood flow rate, aretypically 14-17 gauge, and are already pushing the tolerance of mostpatients.

The patient is then dialyzed for a period specified by the nephrologist.Every 15-30 minutes the patient is monitored for pulse, temperature, andblood pressure, and the functions of the machine are also noted andrecorded on the patient's chart. Monitoring the patient closely,especially for blood pressure, is important because, as previouslystated, a significant number of dialysis patients have very fragilecardiovascular systems and about 25% of all hemodialysis proceduresresult in hypotensive episodes owing to the rapidity of removing in 2-4hours the fluid which has been accumulated over 2-3 days. Most of thepatients have prodromal symptoms before hypotensive episodes butsometimes the episode occurs suddenly, without warning and patient"crashes", losing consciousness. Most of the "crashes" happen during thesecond half of hemodialysis sessions. The standard treatment for suchblood pressure "crashes" is for the nurse of partner to open up the IVadministration line connecting the saline bag to the arterial blood setand to infuse the saline in order to improve the patient's circulatoryvolume and bring the pressure back up. Slower ultrafiltration helps toreduce incidence of crashes. Therefore, my standard practice is toremove no more than one liter of ultrafiltration per hour. The "crashes"are less frequent if controlled ultrafiltration machines are used.

Another common occurrence during hemodialysis happens when the arterialneedle sucks up against the interior wall of the blood vessel eitherbecause of the suction generated by the blood pump or because thepatient changes his/her arm position. This creates excessive negativepressure in the pre-pump segment of the arterial line which, ifmonitored by the machine, will trip an alarm and shut off the blood pumpuntil someone repositions the needle and/or arm and restarts the pump.This, of course, wastes time and lengthens the procedure. If thepre-pump pressure is not monitored, then as suction increases, the bloodflow rate diminishes dramatically and the amount of dialysis expecteddoes not in reality occur. Moreover, the endothelium (internal bloodvessel wall lining) is damaged by suction, which predisposes to clottingand reduces fistula longevity.

At the end of the treatment, the arterial needle is removed, the salineline opened, and the pump started in order to flush the blood remainingin the extracorporeal circuit back to the patient. Most patients arevery anemic (the kidneys control the production of new red cells) and,therefore, retrieval of as much blood as possible is important. Sinceflow is always in the same arterial to venous direction through thecircuit, some practitioners will insert the arterial needle into thesaline bag so the few inches of tubing between the needle and the salineinfusion port will also be flushed.

When the blood is mostly out of the extracorporeal circuit, the venousneedle is removed from the patient, and a compress is applied to thepuncture site until it clots, which may be 10-20 minutes depending onthe size of the needles and the degree of systemic anticoagulation atthe end of the treatment. At this point, the needles and blood lines arediscarded (in biohazard containers) as these components are rarelyreused.

The majority of dialyzers are, however, reused. There are numerousprocedures for reusing dialyzers both manually and automatically. Incenters, special machines for simultaneous multiple dialyzerregeneration are used. Generally the steps are as follows:

1. High flow rate water flush of blood compartment.

2. Force water through the membrane in dialysate compartment to bloodcompartment direction (reverse ultrafiltration).

3. Removal of residual blood and protein by flushing blood compartmentwith bleach and/or peroxide.

4. More water flush.

5. Measurement of remaining fiber bundle volume or the ultrafiltrationrate as an indicator of remaining dialyzer efficiency.

6. Filing, capping, and storing the dialyzer with a chemical sterilantsuch as formaldehyde, peracetic acid, or glutaraldehyde.

7. Documenting all of the above and assuring that there is no chance ofusing a reused dialyzer on a different patient.

Of course, the above procedures must be done in a biohazard environmentsince there is always the potential for exposure to human blood, andhepatitis and AIDS are relatively prevalent in the dialysis population.Also, the OSHA and EPA stipulate various working environment regulationsowing to the hazardous sterilants and cleaning agents used.

Regeneration of dialyzers and lines may be performed on the machine. TheBoag U.S. Pat. No. 4,695,385 discloses a cleaning apparatus for dialyzerand lines. The device is permanently or semi-permanently connected intothe dialysis machine system.

Finally, the dialysis machine plumbing must be periodically cleaned anddisinfected. There are two reasons for this. The first relates to thefact that the dialysate has historically not been sterile. From the verybeginning of dialysis as a therapy, the dialyzer membrane has beenrelied upon to be a sterile barrier between dialysate and blood. This iscertainly true for whole bacteria, but concern has been growing over thepast several years that with the use of synthetic membranes and theirmore porous structure, pyrogens, or components thereof, may bepermeating these membranes and activating inflammatory processes withinthe patients. This may be exacerbated because the pressure gradient isfrequently in the blood-to-dialysate direction when synthetic membranesare used. The second reason is that when bicarbonate containingdialysate is used, calcium carbonate inevitably precipitates andaccumulates on the plumbing and must be dissolved with an acidicsolution.

Clinically, three dialyses per week are associated with rapid changes inbody fluid compartments and in concentrations of all dialyzable solutes.These changes are aptly called "The Unphysiology of Dialysis"(Kjellstrand C M, Evans R L, Petersen R J, Shideman J R, von HartizschB, Buselmeier T J: The Unphysiology of Dialysis: A major cause of sideeffects?" Kidney Int 1975; 7 (suppl 3); S30-S34). Many patients haveenormous difficulties achieving a "dry" body weight if they accumulatethree, four, or more kilograms of fluid between dialyses. Some patients,especially with heart failure, poorly tolerate even a two kilogram fluidweight gain; they are short of breath before dialysis, have musclecramps and hypotension during dialysis, and feel "washed out" and areextremely weak, needing several hours to "equilibrate" and becomefunctional. Serum concentration of highly toxic potassium frequentlyreaches dangerous levels (more than seven mEq/L), particularly precedingthe first dialysis after a longer interval (weekend). To mention only afew others, calcium and pH are too low before dialysis or too high afterdialysis in many patients. Empirically, in many hemodialysis units,these patients are placed on a four times weekly dialysis schedule.

Whereas the normal human kidneys function continuously to produceseamless, gradual changes in total body fluid volume and metabolic wastelevels, three times weekly dialysis schedules produce tremendous,unphysiologic fluctuations which yield considerable stress on thepatient's systems and undoubtedly affects their prognosis.

Historically, artificial kidneys developed according to the assumptionthat the machine should be very sophisticated and automated duringdialysis and less so for preparation and cleansing. This assumption wasvalid for long and infrequent dialysis sessions. Compared to the totaldialysis time the time for setup and cleansing of the machines wasrelatively short.

Another artificial kidney feature that has historical background is aproportioning system of producing dialysis solution and delivering itinto hemodialyzer. In the early years of hemodialysis only a so calledtank system has been used. The machine was provided with a large tankwhere purified water was premixed with dry chemicals to make dialysissolution, which was warmed and recirculated through the dialyzerdialysate path. Bicarbonate was used as a buffer; CO2 was bubbledthrough the solution, or lactic acid was added to the solution toprevent calcium/magnesium carbonate precipitation. With inefficientdialyzers a dialysis time of 12 hours or more was used. Warm dialysatewas an excellent culture medium for bacterial growth. Long dialysis timemagnified the problem. At the end of 11 hour dialysis, even with severalchanges of dialysis solution in the tank, bacterial growth wasstaggering (Twardowski Z, Bahyrycz M, Lebek R, Spett J: Zalety plynudializacyjnego bez glukozy w leczeniuyprezewleklej niewydolnosci nerek.(Advantages of glucose-free dialyzing fluid for hemodialysis treatmentin cases of chronic renal failure.) Pol Arch Med Wewn 1973; 50:1079-1085.). To overcome this problem a proportioning system wasinvented whereby the solution was being prepared ex tempore frompurified water and concentrate. The concentrate contained acetate as thephysiologic buffering agent because bicarbonate tended to precipitatewith calcium and magnesium if present in the same concentrate.

Gradually more efficient dialyzers were designed, and time of a singledialysis session gradually decreased to 8, 6, 5, 4, 3, and even 2 hours.With very efficient dialyzers, acetate was delivered to the patient inexcess of the body ability to metabolize it, which caused cardiovascularinstability. An answer to this problem was to return to bicarbonate as abuffer but within an overall design of proportioning system. Asmentioned before, because of chemical incompatibility of bicarbonatewith calcium and magnesium, two proportioning pumps are required, thefirst to mix the bicarbonate concentrate with water and the second toproportion this mixture with the concentrated electrolytes to achievethe final, chemically compatible solution.

However, a short daily dialysis session of 1-3 hours offers apossibility of abandoning the proportioning system, which continues tobe used out of tradition rather than a necessity. With short dialysisthere is no significant bacterial growth even if the dialysis solutionis premixed in a tank from water and dry chemicals with bicarbonate as abuffer, particularly if the solution flows single pass so that spentdialysate is not mixed with fresh dialysis solution. The spent dialysatethat contains amino acids, vitamins, and other nitrogen products is amuch better medium for bacterial growth than is the dialysis solutioncontaining only electrolytes and glucose.

With daily, in-center hemodialysis, the time and expense now incurred bythe patient and by the staff would be greatly magnified. Also, thedialysis facility's capacity for performing this number of incrementaltreatments would have to be increased, requiring capital expansion. Itis therefore economically and logistically infeasible to do dailydialysis for everybody in-center. Consequently, the patient's home isthe only practical location for this modality.

Whereas at the end of 1980 there were 5,085 such patients (9.7% of thetotal dialysis population), at the end of 1987 only 3,580 (3.6% of thetotal) patients were on home hemodialysis. The home hemodialysispopulation is expected to decrease further in the future because of themany disincentives to this therapy even at a frequency of three timesper week. Increasing the frequency would only exacerbate most of thefollowing disadvantages:

a: Current equipment is big, complicated, intimidating, and difficult tooperate, requiring a very long time for training. Also, both partner andpatient must be trained and this represents a major expense to themedial provider.

b: Complication of equipment engenders reliability issues. If ahemodialysis system breaks down in a patient's home, no dialysis ispossible until it is repaired.

c: It is currently very difficult for home hemo patients to travel sincethe present systems are in no way portable.

d: If the bicarbonate component of the dialysate is used in powderedform, it must be mixed and inspected by the patient.

e: Supplies require a large storage space.

f: There is a high initial investment in the dialysis equipment, thewater treatment system, and their instillation with low utilization (onepatient only) compared to in-center use where the systems are used onmany patients.

g: There is little or no possibility for reuse of supplies, providingless economic incentive to the medical sponsor.

h: a partner is required to insert fistula needles and monitoremergencies.

i: Considerable time is involved for setup, priming, tear down, andcleaning.

j: The water treatment system must also be cleaned/disinfectedperiodically.

Because of the above mentioned disincentives, only highly motivatedpatients and partners undertake the drudgery of home hemodialysis.

Development of a transcutaneous blood access catheter not requiringneedle punctures for each dialysis is currently underway and isdescribed in Twardowski Z J, Van Stone J C, and Nichols W K: MultipleLumen Catheter for Hemodialysis, as described in U.S. Pat. No. 5,209,723assigned to the Curators of the University of Missouri. Such an accessdevice further opens the feasibility of daily hemodialysis.

DESCRIPTION OF THE INVENTION

The features of a new system that overcomes the aforementioned problemswhich currently prohibit daily home hemodialysis are as follows:

1. Built-in water treatment system

For a home (single) dialysis patient a built-in water treatment systeminstead of a separate unit is both portable and economical.

2. Automated Formulation of Batch Dialysis Solution

For the short, daily dialysis procedures herein proposed, bacterialovergrowth is not a problem, and proportioning systems to manufacturethe dialysis solution on-line would no longer be needed. The typicallybicarbonate-based dialysis solution should be prepared from mostly drychemicals and low volume concentrates automatically mixed with treatedwater in a simple, small batch. The elimination of proportioning systemssignificantly simplifies machine design and reduces its cost. Use of drychemicals instead of concentrates lowers transportation cost,considerably decreases requirements for storage space, and lessens theburden on patients.

3. Automated Reuse

The dialyzer and total extracorporeal blood circuit must be reused tokeep the cost of treatment as low as possible. Fortunately, there is awealth of evidence supporting the fact that the reuse of dialyzers doesnot constitute any additional hazard to the patients. Moreover, someavailable data suggests that the reused dialyzers are better toleratedby the patients than those used only once. In addition, if reuse is doneautomatically by the machine, without patient or partner involvement,the burden on their lifestyle will be reduced to attractive levels.

4. Automated Set-up

With daily dialysis, automatic set-up of the machine is important. Thismust include a reusable extracorporeal blood circuit assembly andautomation of the priming of the circuit with sterile, physiologicsolution, in order to minimize the time and effort requirements.

5. Automated Tear Down

The whole process of blood and dialysate circuit cleaning andsterilizing is to be automated.

6. Reduction of storage space requirement

Reuse of dialyzers and lines as well as use of mostly dry chemicalsinstead of concentrates will reduce the need for storage space.

7. Decrease of Elimination of Partner Involvement

A needle-less system, and an ultrashort dialysis with reduction ofdialysis associated symptoms, plus automated set-up and tear down,should eliminate partly or totally partner involvement. Optionally, aremote electronic monitoring of the machine and of the patient's vitalsigns may be used to augment the safety of the procedure.

8. Reduced Training Time

A compact, user friendly machine will reduce training time.

9. Cost Effectiveness

Implementation of all above mentioned features will make the system verycost effective. Total cost will be much lower than in-centerhemodialysis, and should successfully compete with any other method ofchronic dialysis.

DESCRIPTION OF THE INVENTION

In accordance with this invention, hemodialyzer apparatus is providedwhich comprises the following:

Dialyzer membrane means is provided having first and second sides, as isof course conventional. Dialyzate flow path means are provided forpassing dialysis solution across the first side of the membrane means,while blood flow path means are provided for passing blood across thesecond side of the membrane means for dialysis thereof.

A solution storage tank is connected to the dialyzate flow path means.Venous and arterial connector means are carried by the blood flow pathmeans for alternative connection with the vascular system of a patientand with each other through a conventional shunt connector or the like.A water inlet conduit is provided, communicating with water treatmentmeans for processing water from the inlet conduit to purify the water toa condition suitable for use in the hemodialysis apparatus.

A first conduit extends from the water treatment means to receivepurified water therefrom. A second conduit is connected to the firstconduit, and has means for carrying desired amounts of dialysis solutionsolutes, such as lactic acid, potassium chloride, magnesium chloride,calcium chloride, sodium chloride, and sodium bicarbonate.

Thus, a predetermined amount of purified water from the first conduitcan pass through the second conduit and disperse the solutes, which maybe conveyed with the water through further conduit means to the solutionstorage tank, to provide a desired quantity of the dialysis solution ina first operating mode.

A third conduit is also provided, being connected to the first conduitand having means for carrying desired amounts of hemodialyzer apparatusantimicrobial and cleaning agent, such as formaldehyde solutions,hydrogen peroxide, or the like. Thus, a predetermined amount of purifiedwater from the first conduit can pass through the third conduit todisperse the antimicrobial and cleaning agent and to convey it throughthe further conduit means to the solution storage tank, to provide adesired quantity of antimicrobial cleaning solution in a secondoperating mode.

A fourth conduit is also preferably provided, connected to the dialyzateflow path means, and communicating with the blood flow path means, toprovide antimicrobial cleaning solution, and also rinsing solution, tothe blood flow path means in the second operating mode.

Also, valve and control means are provided to selectively andautomatically provide and control fluid flow throughout the apparatus inits various stages of operation.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of the apparatus, showing the dialyzateflow path and other water flow paths; and

FIG. 2 is a diagrammatic view of the blood flow path portion of theapparatus.

DESCRIPTION OF SPECIFIC EMBODIMENTS

The invention is a highly automated system which comprises a relativelysimple hemodialysis system made of the following as shown in thedrawings:

An integral water treatment line and system 10 comprises a coarseparticulate pre-filter (if necessary) 12, a carbon adsorption filter 14,a reverse osmosis membrane 16, a deionizing cartridge 18, and UV light20. Purified water enters the system through a valve 22.

A dialysis solution preparation and delivery system (FIG. 1) isprovided, made of heat resistant materials, capable to withstandrepeated cleanings, and comprising the following.

A 60-90 liter tank 24 has a diaphragm 26 separating a fresh dialysissolution compartment 28 from used dialysate compartment 30. Thediaphragm is leak tight but can move freely so that the increase incapacity of one compartment is associated with the identical decrease incapacity of the other. As is shown in Sausse U.S. Pat. No. 4,029,059,for example, a corrugated, expansible membrane may be used.

A mixing/heating circuit 32 is provided for recirculating fluids in thedialysis solution compartment, heating water, and mixing the chemicalswith water, comprising of inflow line 34, outflow line 36, and bridginglines 38, furnished with valves 22, 40, 42, 44, 46, 48, pump 50, heater52 thermostat 54, and conductometer 56.

A bypass conduit 58 connects inflow line 34 and outflow line 36 of themixing/heating circuit 32 through valves 22, 48 and comprising threelines 60, 62, 64 connected through valves 66, 68.

A salt chamber 70 for dialysis solution chemicals is provided withinflow and outflow tubings 72, 74 connected with the bridging line 38 ofmixing/heating circuit 32 through valve 42, and with the bypass conduit58 through unidirectional valve 66. The chamber 70 contains two cellsfor syringes, one with lactic acid and concentrate of potassium chloride76, and the other with magnesium chloride and calcium chloride 78, andtwo cells for cartridges, one with dry, powdered sodium chloride 80 andthe other with dry, powdered sodium bicarbonate 82. The chamber 70 isprovided with a sensor of fluid level 84 and a vent with valve 86. Thechamber 70 is water tight, but can be opened to add predetermined-weightchanges of dry chemicals, specifically in the form of a cartridgeprovided to the user by the manufacturer.

A chemical chamber 88 is provided for adding cleaning/disinfectingmixture, with inflow and outflow tubings 90, 92 connected with thebridging line 38 of the mixing/heating circuit 32 through valve 44, andwith the bypass conduit 58 through the valve 68. The chamber 88accommodates a cartridge containing conventional chemicals which, whendissolved in water, produce chemical species which will both clean upthe extracorporeal circuit of blood and blood elements and willdisinfect all fluid circuits in the system. This chamber is also watertight, but can be opened for placing new charges of dry chemicals, alsopreferably as commercially manufactured cartridges.

Dialysis solution circuit 94 with inflow and outflow tubings 96, 98 isconnected with the dialysate compartment of the hemodialyzer 100, andthrough the valves 46, 48 with the outflow tubing 36 of themixing/heating circuit 32. Inflow tubing 96 is equipped with athermometer 106, pump 108, and dialysis solution manometer 110. Theoutflow tubing 98, which comprises a proximal and distal segment 102,104, is furnished with a dialysate manometer 112, dialysate clamp 114for regulating dialysate pressure, and dialysate valve 116.

Dialysate tubing 118 carries used dialysate into the dialysatecompartment 30 of the tank 24, being provided with valves 120, 122 andhemoglobin detector 124 for detecting free hemoglobin or red cells inthe effluent dialysate as an indicator of blood leak in the fibers ofthe dialyzer.

A measuring cylinder 126 connected with drain pipe 130 through anoutflow tubing 132 and valve 122. Cylinder 126 is provided with a scale128 and a sensor 134 for respective visual and automatic determinationof the fluid level. During hemodialysis the sensor 134 measuresultrafiltration rate to regulate ultrafiltration by pressure adjustmentin the dialysate and blood compartments of the dialyzer. Cylinder 126 isfilled with fluids through outflow tubing 136 of the dialysatecompartment 30.

A blood/dialysate shunt 138 is provided for connection with anextracoporeal blood circuit, being controlled by valve 120.

Drain pipes 130, 140 are also provided.

The extracorporeal blood circuit 101 (FIG. 2) is made of materialsdesigned to withstand repeated cleanings and to be as biocompatible andnon-thrombogenic as possible, and includes the following.

A hemodialyzer 100, is provided, preferably with high flux and highbiocompatibility characteristics.

Inflow and out flow lines 144, 146 are provided, being for connectionwith respective inflow and outflow lumens 145a, 145b of preferably adouble lumen intravenous catheter implanted in the patient.

A blood pump 148 is provided for moving blood or other fluids within theextracorporeal circuit.

Blood manometers 150, 152 are for determining the pressure in the lines(both inflow and outflow), at the post-pump pre-dialyzer location, andat the post-dialyzer location.

An air trap 154 is present in the outflow line 146 prior to bloodreturning to the patient.

A blood clamp 156 regulates pressure in the blood compartment of thehemodialyzer 100.

An air/foam detector 158 in the outflow line between the air trappingchamber and the patient for closing the line if foam is present.

A detector 160 is provided for detecting the conductivity of anysolution in the circuit.

A coupling means 162 to connect the inflow and outflow blood lines 144,146 in a closed loop is present adjacent the location of the lumens 145of the patient's catheter or arteriovenous shunt.

A saline bag 164 and conduit 166 connects the bag to the inflow line 144of the extracorporeal circuit through a saline valve 168. The valve 168divides the inflow line 144 into proximal and distal segments 170, 172.

An unidirectional blood/dialysate shunt valve 174 connects the outflowline 146 with the dialysate tubing 118 through blood/dialysate shunt 138and valve 120. The shunt valve 174 allows fluids to pass from theextracorporeal blood circuit into the dialysate effluent tubing 118, butprevents fluid passage in the opposite direction.

A microprocessor-based monitoring and controlling system may be providedwhich contains all the logic, receives and processes all commands bycontrolling valves and pumps, monitors and interprets all sensors,activates all alarms, and directs the operation of all aspects of thesystem.

A video display may also be provided with associated electronics,processors and keypads for all communication into and out of themachine.

The first step in this highly automated dialysis procedure is for thesystem to automatically prepare a fresh batch of dialysis solution forthe upcoming treatment. At the end of the previous treatment, thepatient has done three things in preparation for the next treatment.First, he/she sterilizes and cleans manually the salt chamber 70, andinserts syringes with solutions and cartridges with dry chemicals intoappropriate cells. Secondly, the patient inserts an appropriatecartridge into the chemical chamber 88. Thirdly, the patient programsinto the system's memory (via a touch-sensitive display) the time of dayhe/she intends to begin the next treatment. This last step will oftennot be necessary, however, since many patients will dialyze at the sametime every day, and will need only to enter this time once and change itthereafter by exception only. All these tasks will take only a fewminutes.

Knowing the expected start time of the next treatment, the system willbegin preparation of the dialysis solution so that it will be fullymixed, and its quality assured, just before the patient is ready tobegin, thereby minimizing bacterial growth. The salt chamber 70,dialysis solution compartment 28, dialysate compartment 30, dialysatetubing 118, and measuring cylinder 126 are empty at this time. As willbe the case in subsequent modes of operation, water can only enter theblood flow path by passing, first, through an R/O membrane 16 whoseintegrity is continuously assured by conductivity; second, through a UVlight chamber 20; and finally, through the hemodialyzer 100 whosemembrane is restrictive to pyrogens, and whose integrity is assured bythe blood leak detector. In this way, the system essentially guaranteesthat no bacteria or pyrogens will ever enter the patient via this route.

The process starts after internal washing with cleaning solution in theprevious cycle, plus draining all fluid present in the chemical chamber88, mixing/heating circuit 32, bypass conduit 58, and hemodialyzerdialysis solution circuit 94. The system is first flushed withsufficient purified water from line 10 so that any cleaning/disinfectingagents and contaminants remaining from the previous treatment areremoved. After emptying again, the chamber 88, circuits 32 and 94, andbypass conduit 58 are filled with water from line 10. Both circuit pumps50 and 108 are activated so that the pressure in the hemodialyzerdialysis solution circuit 94 is raised, thus pushing water through thehemodialyzer membrane into the blood flow path 101 and dislodging anyremaining blood elements or chemicals. The blood/dialysate shunt valve174 (FIG. 2) allows fluid to flow through the shunt 138 into dialysatetubing 118 for drainage. This process continues for a predeterminedtime. Then the blood pump 148 recirculates the fluid left in the bloodflow path 101 in a countercurrent direction to the circulating water inthe dialyzate flow path 94. Owing to the concentration gradient, anyremaining chemicals from the blood flow path 101 will diffuse into thewater in hemodialyzer dialysis solution circuit 94. The valves 116, 120,and 122 direct the water to the drain pipe 130. Once conductometer 160shows that there are no chemicals left in the extracorporeal circuit,the blood/dialysate shunt valve 174 closes, and all water is drainedfrom the whole dialysis solution preparation and delivery system of FIG.1.

At a predetermined time before the next use, the dialysis solutioncompartment 28 of the tank 24 is filled with purified water through line10. The diaphragm 26 is pushed by the water to maximize capacity of thedialysis solution compartment 28 and minimize capacity of the dialysatecompartment 30. Valves 22, 40, 42, 44, 46, 48, 66, 68, 116, 120, and 122are arranged in such positions that water fills the mixing/heatingconduit 32, bypass conduit 58, hemodialyzer dialysis solution circuit94, dialysate tubing 118, and dialysate compartment 30 of the tank 24.The measuring cylinder 126, and both chambers 70 and 88 remain fluidfree at this time, as controlled by valves 42, 44 and 122. Then afterthe above enumerated circuits, conduits, tubings and compartments arecompletely filled with water, water enters the measuring cylinder 126through the outflow tubing 136, and the sensor 134 in the measuringcylinder 126 causes the valve 22 to close. Then the valves 46 and 48close entrance into the hemodialyzer dialysis solution circuit 94. Pump50 is activated to circulate water in the mixing/heating circuit 32which includes lines 34, 38, 36, and dialysis solution compartment 28 ofthe tank 24. The water is warmed by the heater 52 to the desiredtemperature set on the thermostat 54.

Once the desired temperature is achieved, valve 42 directs water throughthe tubing 72 into the salt chamber 70, and the air is expelled throughthe vent 86. Once the water fills completely the chamber as indicated bythe sensor 84, the vent 86 is closed, and the valve 66 assumes such aposition as to allow water flow through the chamber 70 and outflowtubing 74 into the bypass conduit 58 to tank compartment 28. Thedepletion of fluid in the dialysis solution compartment as chamber 70fills causes the diaphragm 26 to move and to lower the level of fluid inthe dialysate compartment 30.

As water passes through chamber 70, lactic acid and concentrates areautomatically injected from the syringes 76, 78 into the water, and thecartridges 80, 82 with powdered chemicals are automatically opened andmixed with the flowing water. Recirculation of fluid continues for apredetermined time to guarantee complete dissolution of dry chemicals.

Once the correct concentration of dialysis solution electrolytes isassured by conductometer 56, valve 42 closes the inflow tubing 72 of thechamber for dialysis solution chemicals 70. Air vent 86 opens, and thefluid is completely drained from the chamber. The diaphragm 26 is thusmoved to overfill the dialysate compartment 30 which activates sensor134 in the measuring cylinder 126. The sensor 134 causes the valve 66and vent 86 to close.

Then, the valves 46 and 48 open the dialysis solution circuit 94. Thepump 108 is activated, and the dialysis solution is circulated, in aclosed loop fashion, through the hemodialyzer 100, along lines 102, 104,and 58 back into the mixing/heating circuit 32. Then the solution flowsthrough lines 38, 96 to complete the circuit.

Simultaneously, the sterile water left in the blood flow path 101 by theprevious flushing step is recirculated in a countercurrent direction tothe dialysate using the blood pump 148. Owing to the concentrationgradient, electrolytes from the dialysate will diffuse through thedialysis membrane into blood flow path 101 until the concentration ofall ionic species is in equilibrium. The extracorporeal circuit is thusautomatically primed with sterile, non-pyrogenic, physiologic solution.This process takes just a few minutes and, during this time, the rate ofconductivity rise in the extracorporeal circuit is monitored byconductometer 160 and used to establish first the clearance propertiesof the dialyzer. This, in turn, is used to determine when theperformance of dialyzer 100 has decayed to a point that it should bereplaced, and second, when equilibrium is achieved and priming iscomplete.

An electronic display will indicate to the patient that priming iscomplete, and that it is possible to start dialysis. The patient opensboth solute chambers 70 and 88, drains residual fluid (if present),inspects whether all chemicals have been completely dissolved, andremoves spent cartridges and syringes. If the inspection verifies propermachine function, the patient measures his/her weight, blood pressure,pulse and temperature, and enters data into a flow-sheet and the systemmemory together with intended ultrafiltration, duration of dialysis,blood and dialysate flow. Then the patient removes spent saline bag 164and replaces with a new one, and touches the display to activate thesaline flushing cycle. The machine drains a predetermined amount ofsaline through the saline conduit 166 and valve 168, coupling means 162,blood dialysate shunt valve 174 and shunt 138 into dialysate tubing 118to flush the freshly made connection from possible contaminants, andthen changes position of the saline valve 168.

The patient activates the blood pump 148 to flush more saline throughthe hemodialyzer 100 and into the blood/dialysate shunt 138. The patientopens inflow and outflow lumens of his catheter 145, which typically maybe of the intravenous double lumen type so that needle sticks are notrequired. The patient assures the free flow of blood, and injectsheparin into both lumens. Finally, the patient removes the couplingmeans 162 from the inflow and outflow lines 144, 146, and connects thelines to his/her catheter inflow and outflow lumens 145, using aseptictechnique. When the connections are made, the patient touches thecontrol display to so indicate.

The machine now begins to draw blood into the arterial blood line 144while the priming solution is directed through the blood/dialysate shunt138 to dialysate tubing 118. After a predetermined amount of blood isdrawn into the circuit, the priming solution is directed back to thepatient by means of valve 174 to prevent any blood loss through theblood/dialysate shunt 138. As an additional security measure, thehemoglobin detector 124 will stop the blood pump 148 if any blood orhemoglobin enters the dialysate tubing 118. Finally, the patientobserves the function of the blood/dialysate shunt valve 174 and canstop the procedure manually if blood enters the blood/dialysate shunt138.

The measuring cylinder 126 (FIG. 1) is emptied through the outflowtubing 132, valve 122, and the drain pipe 130 at that time. The speed ofpump 148 is increased to the prescribed value. Valves 48 and 116 shutoff return of dialysate to circuit 32 and direct spent dialysate intothe dialysate tubing 118. The dialysis solution is pumped single-passthrough the dialysate compartment of the dialyzer, countercurrently tothe blood flow, and then into the spent dialysate compartment 30 of thetank 24 through the dialysate tubing 118 for measuring volume. Anincrease of fluid volume coming out of dialyzer 100 over the fluidvolume going into dialyzer 100 can be measured in cylinder 126 tomonitor ultrafiltration. In the case where hypotension is detected bypatent's prodromal symptoms and confirmed by blood pressure measurement,the blood from the dialyzer will be returned to the patient through theoutflow line 146 and sterile saline will be drawn from the bag 164 intoinflow line 144. This saline addition continues until the pressurenormalizes, and the normal dialysis procedure can continue. With dailytreatments and controlled ultrafiltration, the incidence of hypotensionwill be virtually eliminated in most patients as described above.

At a predetermined time the display alerts the patient that thetreatment is completed. The patient touches the display to initiate theprocess of dialysis termination. The blood pump 148 stops. The salinevalve 168 connects the saline conduit 166 exclusively with inflow line144, and the saline from the bag 164 pushes blood back to the patientthrough the proximal segment 170 of the inflow line 144 and the inflowlumen 145a of the patient's catheter. After a predetermined volume ofsaline is infused, the saline valve 168 closes the connection of thesaline conduit 166 with the proximal segment 170 and opens connection ofthe conduit 166 exclusively with the distal segment of the inflow tubing172. The blood pump 148 is activated. As the remaining blood is pumped,pump 148 pulls saline into the distal segment 172 of the inflow line144, the blood compartment of hemodialyzer 100, the outflow line 146,and back into the patient through the outflow lumen 145b of thepatient's catheter. In the meantime, the patient clamps the inflow lumen145a of the patient's catheter. After predetermined volume of saline isinfused, the blood pump 148 is stopped. The patient controls the processof blood return and can correct it manually, if needed.

When no blood is visible in the outflow line 146 the patient clamps theoutflow lumen 145b of his catheter, disconnects the system tubing, andtouches the display to indicate that the process ofcleaning/disinfecting may be initiated.

The machine automatically starts the process of cleaning. In themeantime the patient fills both of his catheter 145 lumens with heparin,secures both lumens with clamps and caps, measures his/her weight, bloodpressure, pulse, temperature, and total ultrafiltration and enters datainto the flow/sheet and the system memory. Finally, as mentionedearlier, the patient sterilizes and cleans manually the chambers 70, 88,inserting syringes with solutions and cartridges with dry chemicals intoappropriate cells. The patient also inserts an appropriate cartridgeinto the cleaning chemical chamber 88, and programs the time of day ofthe intended next treatment.

The process of cleaning starts by creating high pressure on the dialysissolution side of dialyzer 100, thus pushing solution through thedialyzer membrane and dislodging blood elements that may haveaccumulated in the pores or on the membrane during the treatment.Blood/dialysate shunt valve 174 directs fluid in blood circuit 101through the shunt 138 into dialysate tubing 118. This process continuesuntil a predetermined volume of dialysate has been used to flush theextracorporeal circuit. Finally a remaining volume of saline from bag164 is flushed through the blood compartment of the hemodialyzer 142 toremove the dislodged blood elements and rinse them toward shunt 138 andultimately drain 130.

Next, the blood/dialysate shunt 138 is closed, and all fluid is drainedfrom the whole dialysis solution delivery system by setting valves inappropriate positions. Then, the dialysis solution compartment 28 of thetank 24 is filled with purified water from line 10. The diaphragm 26 ispushed by the water to maximize capacity of the dialysis solutioncompartment 28 and to minimize capacity of the dialysate compartment 30.Valves 22, 40, 42, 44, 46, 48, 66, 68, 116, 120, and 122 are arranged insuch positions that water fills the mixing/heating conduit 32, bypassconduit 58, hemodialyzer 10, dialysis solution circuit 103, dialysatetubing 118, and dialysate compartment 30. The measuring cylinder 126,and both chambers 70 and 88 for chemicals remain fluid free at thistime. Once the desired circuits, conduits, tubings and compartments arecompletely filled with water, the sensor 134 in the measuring cylinder126 causes the valve 22 to be shut. Then the valves 46 and 48 closeentrance into the hemodialyzer dialysis solution circuit 94, and pump 50is activated to recirculate water in the mixing/heating line 32, conduit38 and dialysis solution compartment 28. The water is warmed by theheater 52 to the desired temperature set on the thermostat 54. Once thedesired temperature is achieved, valve 44 directs water through theinflow tubing 90 into chemical chamber 88, and then through the outflowtubing 92 and valve 68 into the bypass conduit 58 and then compartment28. Recirculation of fluid continues for a predetermined time toguarantee complete dissolution of dry chemicals from chamber 88.

Once the dissolution of the chemicals is assured by conductometer 56,valves 46 and 48 open the hemodialyzer dialysis solution circuit 94.Pump 108 is activated, and the dialysis solution is recirculated, in aclosed loop fashion, through hemodialyzer 100 and through themixing/heating circuit 32. Simultaneously, the saline left in blood flowpath 101 circuit by the previous flushing step is recirculated in acounter current direction to the dialysate using the blood pump 148.Owing to the concentration gradient, cleaning/disinfecting chemicalsfrom the dialysate will also diffuse into blood flow path 101 until theconcentration of all solutes is in equilibrium. The dialysate valve 116allows passage of fluid into dialysate tubing 118 and dialysatecompartment 30 of the tank to flow countercurrently to the fluid in theblood compartment of the hemodialyzer. After total amount of fluid istransferred from the dialysis solution compartment 28 into the dialysatecompartment 30, the dialysis solution compartment 28,heating/disinfecting circuit 32, and bypass conduit 58 are drained, andflushed twice with water through appropriate positions of valves 22, 40,48, 66, 68, and 86.

Finally the pump 50 is activated to recirculate water in themixing/heating circuit 32, bypass conduit 58, and dialysis solutioncompartment 28 of the tank 24, and the water is warmed by the heater 52to the desired temperature set on the thermostat 54. Once the desiredtemperature is achieved, the positions of valves 22 and 48 are changedto allow complete drainage of water from the dialysis solutioncompartment 28. Finally, the valves 22 and 48 completely close thedialysis solution compartment. At this instant the dialysate compartment30 and measuring cylinder 126 are drained completely of fluids. Theposition of the valves 22, 48, 116, 120, and 122 is changed to allowmore water to enter into and recirculate in the mixing/heating circuit32 bypass conduit 58, and pass through distal segment 104 of the outflowtubing 102 of the hemodialyzer dialysis solution circuit 94, intodialysate compartment 30. Once the dialysate compartment is overfilledwith water, the valves 22, 44, 46, 48, and 68, change positions to allowfluid to recirculate in mixing/heating circuit 32, bypass conduit 58,and the chamber for cleaning/disinfecting chemicals 88. The solutionpresent in this chamber still contains cleaning/disinfecting chemicalsand becomes slightly diluted. The position of valves 46, 48, and 116changes again so that the solution will slowly recirculate in themixing/heating circuit, bypass conduit 58, and hemodialyzer dialysissolution circuit 94. Also, the blood pump 148 will slowly recirculatethe fluid in blood flow path 101. The presence of disinfectant and fluidmovement restrains bacterial growth, and continues until the time of thenext treatment.

Typically after one month of use, the whole extracorporeal blood circuitis replaced by a new one. The frequency of replacement of watertreatment filters will depend on the local quality of water.

Optionally the system may be provided with automated vital signs andmachine monitoring equipment. These may be connected with a centralmonitoring service (or dialysis facility) to remotely monitor thepatient and the instrument during the treatment, thereby obviating theneed for a partner in most cases.

The inflow line 96 of the hemodialyzer dialysis solution circuit 94 maybe provided with a depyrogenation filter.

Powdered glucose may be used additionally for dialysis solutionpreparation.

Ozone may be used as disinfecting agent, and an ozone generator may beincluded in the cleaning/disinfecting chamber.

The salt chamber may be cleaned and sterilized automatically. In such acase the patient inserts syringes and cartridges into the salt chamber8-12 hours after termination of dialysis.

I have been interested in an influence of dialysis frequency on symptomsof uremia for many years. In 1974 and 1975, I published three papersdealing with the adequacy of hemodialysis (Twardowski Z: "The adequacyof hemodialysis in treatment of chronic renal failure." Acta Med Pol1974; 15: 227-243. Twardowski A: "Significance of certain measurableparameters in the evaluation of hemodialysis adequacy." Acta Med Pol1974; 14: 245-254. Twardowski A: "Effect of long-term increase in thefrequency and/or prolongation of dialysis duration on certain clinicalmanifestations and results of laboratory investigations in patients withchronic renal failure." Acta Med Pol 1975; 16: 31-44.). I have alwaysobserved improvement in the patient's well-being with an increase infrequency of dialysis. The results were so impressive I concluded thelast paper of this series with the statement: "It seems that dailyshort-lasting dialysis will be, in the near future, the basic form oftreatment of uremia." In these studies, I did not try more than fourweekly dialyses.

In later years, I applied daily short dialysis in many patients, butonly in connection with the additional stress of surgery, trauma, orinfection and daily dialysis was applied usually for only one or twoweeks.

Teschan et al. (Teschan P E, Ahmad S, Hull A R, Nolph K D, Shapiro F I:"Daily dialysis--applications and problems." Trans Am Soc Artif InternOrgans 1980; 26: 600-602.) explored theoretically the rationale andtechnical and logistical requirements for implementation of dailydialysis. They concluded that it "is not routinely indicated byavailable information and experience in either acute or chronic renalfailure;" however, they stressed that "On the other hand it may behelpful if feasible and does not result in injury to patients or producedepletion syndrome or other evidence of illness."

Extensive evaluation of daily dialysis have more recently been performedby Buonacristiani et al. (Buonacristiani U, Quintaliani G, Cozzari M,Giombini L, Ragaiolo M: "Daily dialysis: Long term clinical metabolicresults." Kidney Int. 1988; 33 (suppl 24): S137-S140.). These studiesshowed an excellent intradialytic tolerance with dramatic decreases inmost symptoms of dialysis, including incidence of hypotension, cramps,headaches, and asthenia. Blood pressure normalized in all patients,hematocrit increased, and nerve conduction velocity slowly improved. Allpatients enjoyed improved general well-being, increased appetite andmuscular strength, and some patents reported improved sexual function.The evolution of CAPD in the late 1970's and early 1980's was widelyhailed for its ability to decrease some of the same symptoms. However,the improvement effected by CAPD over three times weekly HD pales incomparison to the improvement demonstrated by Buonacristiani, et al.

A striking improvement in intradialytic tolerance during dailyhemodialysis has also been reported by Hombrouckx et al. (Hombrouckx R,Bogaert A M, Leroy F, Beelen R, de Vos J Y, Van Overmeeren G, VerhoevenR, Verdonck P, Vercruysse V: "Limitations of short dialysis are theindications for ultrashort daily auto dialysis.: ASAIO Trans 1989; 35:503-505.).

Recently I have started a study in three patients to compare theclinical and metabolic consequences of change from routine chronic,thrice weekly hemodialysis to daily hemodialysis. Similar to others, Iobserved a dramatic improvement in general well-being, almost completedisappearance of all symptoms of intradialytic intolerance and postdialysis weakness. During the 6 months of daily hemodialysis schedule(504 treatment sessions) only 19 (3.8%) mild hypotensive episodesoccurred in these 3 patients, where during the preceding 3 months (144treatment sessions) 23 (16%) of such episodes, including 3 (2.1%) severe"crashes", were noted. Again, dramatic improvements in control of bloodchemistries and blood pressure were observed.

Owing to the automation, the time and effort involvement on the part ofthe patient will be drastically reduced. The machine does most of thework. Eliminated or markedly simplified are:

The time traveling to and from the dialysis clinic,

Mixing of dialysate,

Assembly of the extracorporeal circuit,

Priming of the extracorporeal circuit,

Recirculating priming solution to dialyze, away reuse contaminants.

Testing for residual disinfectant,

Manual rinseback of blood,

Disassembly of the extracorporeal circuit,

Manual reuse of the dialyzer and bloodlines,

Cleaning and disinfecting the plumbing,

Cleaning and disinfecting the water treatment system.

Also, if the patient is employing a permanent catheter instead ofneedles, there will be no need to (painfully) insert them or to hold acompress on the puncture sites at the end of the treatment and waituntil clotting occurs. In addition, the catheter should yield fasterblood flow rates and fewer negative pressure alarms and thereforeshorter treatment times.

The involvement of a partner can be eliminated completely or at the veryleast reduced significantly because of:

No needles to insert,

Reduced Symptoms,

Optional remote vital signs monitoring and machine control system.

The time, intelligence, and motivation required to learn the operationof the instrument and the dialyzing procedures are significantlyreduced.

The system's self-contained compact design would allow travel.

The space in the patient's home previously required for supplies, watertreatment system, and dialysis machine are significantly reduced.

The small batch, positive pressure design will eliminate manycomplicated subsystems of current dialysis instruments and shouldtherefore, result in a much more reliable system. Use of dry chemicalsinstead of concentrates decreases cost and saves storage space.

The automation inherent in the design as well as the user friendlydisplay will significantly enhance learning and operating the system.

The integrated water treatment system and compact size should allowportability and therefore travel.

The above has been offered for illustrative purposes only, and is not tobe interpreted as limiting the scope of the invention, which is asdescribed in the claims below.

That which is claimed:
 1. A hemodialyzer apparatus, which comprises:adialyzer membrane having first and second sides; a dialyzate flow pathfor passing dialysis solution across the first side of said membrane; ablood flow path for passing blood across the second side of saidmembrane for dialysis thereof; a solution storage tank connected to saiddialyzate flow path and having capacity large enough to holdsubstantially all dialysis solution used in a clinical dialysisprocedure; venous and arterial connectors carried by said blood flowpath for connection with the vascular system of a patient; a water inletconduit communicating with water treatment apparatus for processingwater from said inlet conduit, to purify said water to a conditionsuitable for use in said hemodialyzer apparatus; a first conduitcommunicating with said water treatment apparatus and said storage tank;a second conduit connected to said first conduit, said second conduitbeing connected to apparatus for carrying desired amounts of dialysissolution solutes, and a valve selectively causing the entire flow ofwater from said first conduit to pass through said second conduit in afirst operating mode to disperse said solutes; a further conduit systemfor conveying water and solutes contained therein from said secondconduit to said solution storage tank to provide a desired quantity ofsaid dialysis solution in said first operating mode; and a valve andcontrol system to selectively and automatically provide and controlfluid flow from the tank to the dialyzate flow path and throughout saidhemodialyzer apparatus.
 2. The apparatus of claim 1 in which a fourthconduit, connected between said dialyzate flow path and said blood flowpath, plus a one way valve, are provided to selectively permit one wayflow of cleaning and rinsing solution from said blood flow path to saiddialyzate flow path.
 3. The apparatus of claim 1 in which said secondconduit comprises a separate solute receptacle for solid, powdereddialysis solution solute.
 4. The apparatus of claim 3 in which saidsecond conduit comprises solute receptacles containing sodium chloride,sodium bicarbonate, and at least one added receptacle for other dialysissolution solutes.
 5. The apparatus of claim 1 in which said secondconduit comprises apparatus for holding syringes for injecting liquidsolute concentrate into said second conduit.
 6. The apparatus of claim 1in which access to a patient's blood supply takes place through aneedleless system.
 7. The apparatus of claim 1 which also comprises athird conduit, connected to said first conduit, having apparatus forcarrying desired amounts of hemodialyzer apparatus cleaning agent plus areceptacle for containing said agent to permit purified water from thefirst conduit to pass through said third conduit and to disperse saidagent and to convey it to said solution storage tank to provide adesired quantity of antimicrobial cleaning solution in a secondoperating mode.
 8. A hemodialyzer apparatus, which comprises;a dialyzermembrane having first and second sides; a dialyzate flow path positionedfor passing dialysis solution across the first side of said membrane; ablood flow path positioned for passing blood across the second side ofsaid membrane for dialysis thereof; a solution storage tank connected tosaid dialyzate flow path and having a capacity large enough to holdsubstantially all dialysis solution used in a clinical dialysisprocedure; venous and arterial connectors communicating with said bloodflow path for communication with a vascular system of a patient; a waterinlet conduit; a first conduit communicating with said tank and saidwater inlet conduit to receive water therefrom; apparatus forautomatically providing desired amounts of dialysis solution solutes tosaid water in a manner providing water containing said dialysis solutionsolutes in dispersed form in said solution storage tank, to thus providea desired quantity of said dialysis solution in a first operating mode;and valve and control means to selectively and automatically provide andcontrol fluid flow throughout the apparatus; said hemodialyzer apparatusalso comprising a third conduit, connected to said first conduit, havingapparatus for carrying desired amounts of hemodialyzer apparatuscleaning agent plus a receptacle for containing said agent to permitpurified water from the first conduit to pass through said third conduitand to disperse said agent and to convey it to said solution storagetank to provide a desired quantity of antimicrobial cleaning solution ina second operating mode.
 9. The apparatus of claim 8 having a fourthconduit connected between the dialyzate flow path and said blood flowpath, plus a valve to permit flow of aqueous solution from said bloodflow path to said dialysate flow path in a second, cleaning mode ofoperation of the hemodialyzer apparatus.
 10. The apparatus of claim 8,having a fourth conduit connected between said dialyzate flow path andsaid blood path, plus one way valve means to selectively permit one wayflow of solution from said blood flow path to said dialyzate flow pathduring a second cleaning mode of operation of the hemodialyzerapparatus.
 11. The apparatus of claim 8 which further comprisesapparatus providing access between a patient's blood supply and theblood flow path, said access apparatus comprising a needleless system.12. The apparatus of claim 8 which further comprises a source of normalsaline solution to the blood flow path, said valve and control meansselectively permitting flushing of the saline solution through the bloodflow path in one mode of operation to at least one of the venous andarterial connectors to maximize blood return to the patient.
 13. Theapparatus of claim 8 which further comprises an ultrafiltrationregulating system which automatically measures the volume of dialysissolution by monitoring of an overflow measuring container.
 14. Theapparatus of claim 8 which further comprises a conductivity detectorpositioned to measure the conductivity across said blood flow path. 15.A hemodialyzer apparatus, which comprises:a dialyzer membrane havingfirst and second sides; a dialyzate flow path positioned for passingdialysis solution across the first side of said membrane; a blood flowpath positioned for passing blood across the second side of saidmembrane for dialysis thereof; a solution storage tank connected to saiddialyzate flow path and having a capacity large enough to holdsubstantially all dialysis solution used in a clinical dialysisprocedure; venous and arterial connectors communicating with said bloodflow path for connection with the vascular system of a patient; a waterinlet conduit communicating with a water treatment system for processingwater from said inlet conduit, to purify said water to a conditionwherein said water is substantially purified water; a first conduitcommunicating with said water inlet conduit and said storage tank;apparatus for automatically providing desired amounts of dialysissolution solutes to said purified water to provide said dialysissolution containing said dialysis solution solutes in dispersed form insaid solution storage tank, to thus provide a desired quantity of saiddialysis solution in a first operating mode; a second conduit connectedto said first conduit, said second conduit being connected to saidapparatus for carrying desired amounts of dialysis solution solutes, anda valve selectively causing the entire flow of water from said firstconduit to pass through said second conduit in said first operating modeto disperse said solutes; a further conduit system for conveying waterand solutes contained therein from said second conduit to said solutionstorage tank to provide a desired quantity of said dialysis solution ina first operating mode; and a valve and control system to selectivelyand automatically provide and control fluid flow from the tank to thedialyzate flow path and throughout the hemodialyzer apparatus.
 16. Theapparatus of claim 15 which further comprises a source of aqueoussolution to the blood flow path to selectively permit flushing of theaqueous solution through the blood flow path in one mode of operation,through another conduit connected between said dialyzate flow path andsaid blood flow path, to pass cleaning solution from said blood flowpath to said dialyzate flow path for discard in a second operating mode,said another conduit having a flow valve.
 17. The apparatus of claim 1in which said solution storage tank has a volume of 60-90 liters. 18.The apparatus of claim 8 in which said solution storage tank has avolume of 60-90 liters.
 19. The apparatus of claim 15 in which saidsolution storage tank has a volume of 60-90 liters.
 20. The apparatus ofclaim 15 in which said solution storage tank has a volume of at least 60liters.